Biogenic amines play key roles in neurotransmission, metabolism, and in control of various physiological processes. Ring- fluorinated analogs have proved to be powerful tools for the study of the mechanisms of transport, storage, release, metabolism, and modes of action of these amines since they simulate the geometries of the natural compounds so well. By virtue of its very small size and high electronegativity, fluorine is a very favorable replacement for hydrogen in these analogs. In 1970, we developed novel methods for the introduction of fluorine into organic molecules and have applied these methods to the syntheses of a wide variety of biogenic amines with fluorine at various ring-positions. The biological properties and usefulness of these ring-fluorinated biogenic amines have proved to be extremely rewarding and continue to find applications in a multitude of studies. Of particular significance was the discovery that 6-fluoronorepinephrine is a selective alpha-adrenergic agonist and 2-fluoronorepinephrine is a selective beta-adrenergic agonist. Various explanations for the role of fluorine in creating such selectivities have been considered and discarded. Proposals under current consideration include a critical dipole-dipole repulsion between the benzylic hydroxyl group and fluorine in the 2- and 6-positions. This interaction could lead to side-chain conformation preferences favorable for interaction with the beta and alpha adrenergic receptors, respectively. Effects of fluorine on the electronic properties of the aromatic ring are considered also to be important in defining selectivities. Experiments to differentiate between conformational and electronic effects have been initiated. Biological properties of new analogs, including fluorinated epinephrines have mechanistic significance. The use of 18F-labeled 6-fluorodopamine, the biological precursor to 6- fluoronorepinephrine, has been found to be an excellent scanning agent for peripheral noradrenergic innervation.